1. Technical Field
This invention relates reversible inhibitors of the Cathepsin-S which are useful in the treatment of autoimmune and other diseases.
2. Background Information
Cathepsin-S, and compounds active as inhibitors of the Cathepsin-S have been described elsewhere. See for example WO2004083182. A step thought to be critical in autoimmune diseases is the display of self-antigen on the surface of antigen presenting cells (e.g. B-cells) by MHCII. Before presenting antigens to the CD4+ T cells, the antigen binding groove of MCHII is occupied by a protein called P10. Apparently critical to allowing the self-antigen to be displayed on the B-cell surface, the protease Cathepsin-S is involved in cleaving P10 to a lower affinity peptide called CLIP, which can be displaced by the antigenic peptides. Thus by blocking Cathepsin-S with a small-molecule inhibitor may prevent the display of self-antigen, and ameliorate the disease or symptoms of autoimmune or inflammatory diseases. There is presently a large unmet medical need for treatments of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, atherosclerosis, and inflammatory diseases such as chronic obstructive pulmonary disease.